These investigations are concerned with the processes and control of lymphoid differentiation, beginning with multipotential stem cells and ending with the mature T and B lymphocytes which mediate immune defense. An important part of these studies is to compare and contrast normal differentiation with the defects which occur in malignancy and in immunodeficiency diseases. Using organ and cell culture techniques we will attempt to define discrete steps in B-cell differentiation from stem cells to mature lymphocytes. These studies will depend on the use of markers to identify stages of B cell differentiation, including pre-B cells and immature B cells, and on correlation of markers with functional activity. B lymphoma cells will be compared with normal lymphocytes as regards mobility of cell-membrane receptors and differentiation capacity when stimulated by mitogens. These studies will be performed using human lymphomas and the avian lymphoid leukosis model. Using in vitro assays, we will continue to study the biological characteristics of two distinct subpopulations of human T cells which express receptors for IgM (T.M subpopulation) or for IgG (T.G subpopulations). These studies will concern T.M and T.G cells from individuals who are normal, have lymphoid malignancies or have primary immunodeficiency diseases. BIBLIOGRAPHIC REFERENCES: Burrows, P.D., Lawton, A.R. and Cooper, M.D.: Effects of anti-mu suppression and cyclophosphamide on pre-B cells in mice. Fed. Proc. 1977. In press. Hayward, A.R., Simons, M., Lawton, A.R., Cooper, M.D. and Mage, R.G.: Pre-B and B cells in rabbits: Ontogeny and allelic exclusion. Fed. Proc. 1977. In press.